A real world longitudinal study of anaemia management in non dialysis dependent chronic kidney disease patients: a multinational analysis of CKDopps

Non-dialysis-dependent chronic kidney disease (NDD-CKD) patients commonly suffer from anaemia. Anaemia is well known to decrease the quality of life, as well as increase morbidity and mortality. Replacement therapy with erythropoiesis-stimulating agents (ESAs) is available for over 30 years. But the optimal algorithm for anaemia management, including triggers of treatment initiation, medication choice, and target biochemical levels to prevent possible adverse effects remain controversial.
The author Marcelo Barreto Lopes and colleagues conducted a study published in the Nature Journal under the title “A real world longitudinal study of anaemia management in non dialysis dependent chronic kidney disease patients: a multinational analysis of CKDopps”. The summary of this study is below:

Objective:

To outline the factors associated with anaemia treatment initiation and haemoglobin trajectories in patients with NDD-CKD Stage 3 to 5.

Method:

Investigators analyzed 2818 Stage 3-5 NDD-CKD patients, with an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73m2, from Germany, Brazil, and the US. Inclusion criteria: patients naive to anaemia medication [oral iron, intravenous (IV) iron, or ESAs] treatment for the last six months before the study. Patients were divided into two groups: “new users” or “never users,” based on their treatment history and current medications. The study excluded the patients with incomplete or missing medical history questionnaire or medication data. Investigators defined anaemia as Hb<12 g/dL, and used Hb<10 g/dL and<9 g/dL as indicators of low haemoglobin. Similarly, if patients had TSAT<20% or ferritin<100 ng/ml it was considered as iron deficiency (ID).

Findings:

Investigators identified significant insufficient treatment of anaemia, especially in patients with Hb<10 g/dL. Additionally, the treatment in the majority of NDD-CKD patients who had low hematinic measures does not adhere to anaemia practice guidelines and was not provided with conventional anaemia medication within a year. The study reports that oral iron therapy is frequently prescribed, either alone or in combination with an ESA. The initiation of this therapy is guided mainly by haemoglobin levels and to some extent to iron stores. The findings that improve anaemia management for NDD-CKD patients is that at lower Hb, eGFR levels, and presence of comorbidities there is an earlier start of therapy.

Although guidelines often recommend a trial of iron for anaemic patients with TSAT<30% to prevent iron-restricted erythropoiesis; the study found that this population is not commonly treated. IV iron prevents the incident of iron-restricted erythropoiesis more effectively than oral iron and it is prescribed mostly at the advanced stage of CKD.

The patients who have late and infrequent ESA starts or those who have an abundant number of discontinuations during follow-up are at potential risk of overcorrecting Hb and hence exposing patients to adverse effects. On the other hand, there is a chance for the achievement of treatment goals in patients discontinuing both iron replacement and ESAs protocols. Hence, future studies to evaluate a strategy that allows longer treatments at lower doses should be tested.
There was potential for improvement in heart failure patients treated for anaemia and ID. The study also found a similar approach for haemoglobin as described in KDIGO guidelines. A negative slope in Hb is found to be associated with anaemia treatment initiation. While, flat or negative Hb slopes after treatment, denote a lack of response to treatment.

Hence, in real-world practice, the therapeutic options are successful in correcting anaemia in patients with moderate to advanced CKD. The study reported noticeable practice variation across countries.

Limitation:

As it is an observational study, the results should be interpreted with caution. Authors acknowledge future studies that focus on the impact of patient characteristics and their symptom burden related to anaemia, as possible triggers for treatment initiation.

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